Search Results (43)

Diabetes mellitus represents a major global health burden, necessitating the development of safer and more effective therapeutic alternatives. Medicinal plants have gained increasing attention due to their bioactive compounds with potential hypoglycemic and antioxidant effects. The present study aimed to investigate the physicochemical characteristics, phytochemical composition, antioxidant capacity, and toxicological profile of hydroalcoholic tinctures obtained from Agrimonia pilosa Ledeb., Calendula arvensis L., and Polygonum hydropiper L. The tinctures were prepared by simple percolation using 70% ethanol and evaluated according to pharmacopoeial standards, including organoleptic properties, relative density, refractive index, alcohol content, and purity parameters. Phytochemical analysis was performed using thin-layer chromatography and spectrophotometric methods, highlighting the presence of flavonoids and polyphenolcarboxylic acids, with several bands showing chromatographic and spectral similarities to chlorogenic and caffeic acid standards. Antioxidant activity was assessed through total polyphenol and flavonoid content, with Polygonum hydropiper exhibiting the highest values. The hypoglycemic effect was evaluated using the oral glucose tolerance test in normoglycemic mice, demonstrating significant reductions in blood glucose levels, particularly for Agrimonia pilosa at higher doses. Acute toxicity studies indicated a low toxicity profile, with no mortality observed even at high doses (up to 9 g/kg body weight), corresponding to GHS category 5. However, subacute toxicity assessment revealed species-dependent effects, ranging from minimal hepatic changes for Calendula arvensis to moderate hepatotoxicity for Polygonum hydropiper and more pronounced hepatic, renal, and pancreatic alterations for Agrimonia pilosa. These findings suggest that the investigated tinctures possess significant hypoglycemic and antioxidant potential, with generally favorable safety profiles following acute administration. Nevertheless, prolonged use may induce organ-specific toxicity, highlighting the need for further pharmacological and clinical investigations to establish their therapeutic applicability and safety in diabetes management. Full article

The emerging problem that microplastics pose to our society is reflected in the exponential growth in investigations devoted to uncovering their toxicological potential in humans. However, these studies present several limitations, one of the most significant being the use of microplastics that do not represent their environmental counterparts. In this study, we evaluated the impact of two types of polyethylene microplastics (27–32 µm)—non-fluorescent and fluorescent—on the liver and intestine, targeting mitochondria. FVB/n mice were subjected to a subacute exposure to two concentrations representative of human exposure (0.002% (w/w) and 0.006% (w/w)). Both types of microplastics impaired mitochondrial respiration through disruption of NADH-linked pathways, with more pronounced effects at the highest concentration of fluorescent MPs. Electron transport chain complexes, particularly CIII and CIV, were affected, partially explaining the observed alterations in mitochondrial respiratory capacity. An increased SOD and GPx activity supported the link between mitochondrial dysfunction and increased reactive oxygen species overproduction under MPs exposure. Hepatic mitochondrial lipid remodelling was detected following exposure to fluorescent microplastics, while intestinal epithelial cells displayed impaired mitochondrial activity together with compromised cellular integrity, indicative of stress response. In parallel, shifts in gut composition suggest that PE MPs may contribute to intestinal barrier dysfunction. Overall, fluorescent MPs induced more severe mitochondrial and biochemical disturbances in both the liver and the intestine than their non-fluorescent counterparts. Our findings highlight mitochondria as central targets for microplastic-induced toxicity and underscore the need for improved MPs models in toxicological research. Full article

Fluorescent dyes are commonly used as tracers in hydrological investigations to quantify transport pathways, residence times, mixing behavior, and connectivity in surface water, groundwater, and coastal systems. Despite their long history of application, the ecological implications of deliberate dye releases are not well understood. This review synthesizes current knowledge on the physico-chemical characteristics, environmental behavior, and ecotoxicological effects of major dye classes, with emphasis on rhodamines, fluorescein derivatives, and sulfonated xanthene dyes commonly used in water tracing studies. Toxicity data for algae, cyanobacteria, invertebrates, and fish show large inter-specific variability. Some dyes, particularly rhodamine B and eosin Y, show acute or sub-lethal effects at concentrations detected during poorly controlled applications. By contrast, dyes with high polarity and extensive sulfonation (e.g., rhodamine WT, sulforhodamine B, pyranine, and fluorescein) show consistently low toxicity and minimal bioaccumulation potential. Environmental fate processes, including photolysis, sorption, and transformation into potentially more reactive products, influence exposure dynamics, especially in clear, shallow, or slow-moving systems. This review also evaluates regulatory frameworks and operational guidance for safe use, identifies gaps in toxicological and fate data, and proposes recommendations for minimizing environmental impact through dye selection, mass optimization, injection design, and monitoring. The findings support the continued use of fluorescent dyes but highlight the need for more systematic assessment of transformation products, chronic and sub-lethal responses, and cumulative exposure in sensitive environments. Full article

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in a subchronic (90 days, in 2024) oral toxicity rat study. Here, we set out to perform an updated analysis and re-evaluation of these proteomic in vivo data in a comparative manner and in the context of 2-MCPD metabolism, focusing in particular on mitochondrial energy metabolism and the maintenance of the structural integrity and function of the heart. The aim of our project was to develop further reasonable, toxicologically relevant research hypotheses for future studies addressing this topic in order to shed more light on the—so far—rather limited knowledge of the toxicological properties and modes of action of 2-MCPD. Our updated data analysis and comparative re-evaluation revealed strong indications of cytoskeletal protein deregulation, indicative of cardiomyocyte degeneration, and the deregulation of enzyme proteoforms linked to carbohydrate utilization and mitochondrial functions. This led us to hypothesize that reactive metabolites of 2-MCPD, other than those formed from 3-MCPD, could impair mitochondrial pyruvate utilization and mitochondrial energy production, potentially resulting in cardiac functional heart failure in rats at doses slightly higher than 10 mg 2-MCPD per kg bw/day. Thus, we postulate the intermediate formation of some putative aldehydic and acidic metabolites following oral 2-MCPD exposure that might be causative of cardiotoxicity in rats. Full article

Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The present study investigates the early metabolic toxicity of chronic low-dose microcystin-LR (10 µg/L) in a 7-week rat model, specifically focusing on pre-symptomatic perturbations in lipid homeostasis. By integrating biochemical profiling with multivariate systems toxicology (LASSO and PLS-DA), we identified a specific phenotype of “Silent Hepatic Total Cholesterol Accumulation” (T-CHOL +16%, p = 0.01) occurring in the absence of systemic dyslipidemia or overt liver injury. Mechanistic analysis revealed a specific dual failure of cholesterol homeostasis, characterized by the paradoxical upregulation of the influx transporter Ldlr (LASSO coef +0.661) and the suppression of the efflux transporter Abcg1 (PLS1 loading −0.358). Crucially, Ldlr upregulation occurred despite the concomitant transcriptional downregulation of Srebp2 (Spearman ρ = −0.585), indicating a regulatory uncoupling mechanism. We propose that microcystin-LR-induced protein phosphatase 2A (PP2A) inhibition likely drives this uncoupling via a post-transcriptional override—possibly involving ERK/RSK-mediated Ldlr mRNA stabilization. Concurrently, this inhibition appears to block LXR-mediated Abcg1 expression through sustained AMPK hyperactivation resulting from the loss of dephosphorylation. These findings indicate liver-specific cholesterol accumulation as the critical first step of environmental NAFLD pathogenesis, suggesting that current WHO guidelines (1 µg/L) may require re-evaluation regarding metabolic safety. We propose the hepatic Ldlr/Abcg1 ratio as a potential early biomarker for revised risk assessment. Full article

Plantain (Musa paradisiaca L.) is a tropical monocotyledonous, succulent plant of the Musaceae family commonly grown for food in the tropical regions of the African, Asian, and South American continents, where its parts are also sought for ethnomedicinal purposes in the treatment of burns, inflammation, and diabetes, among others. In the present preliminary exploratory study, the ethanol extract of the underutilized Musa paradisiaca peel (MPE) was evaluated for its in vitro inhibitory effects on α-amylase and α-glucosidase, as well as its in vivo hypoglycemic activity and potential biochemical toxicity. MPE (100, 200, 400 mg/kg) was orally administered to normal experimental rats for 30 days, following which the lipid profile, antioxidant status, and serum/tissue indices of hepatic, renal, and cardiac functions were evaluated. MPE produced significant inhibition (p < 0.05) of α-amylase (37%) and α-glucosidase (46%) at 120 µg/mL in vitro. The effect was lower than that of acarbose (IC₅₀ = 44.4 ± 1.14 and 15.60 ± 0.01 µg/mL, respectively). A modest blood glucose-lowering effect of MPE was observed at the highest tested dose (400 mg/kg) following subacute oral administration. During this treatment period, no biochemical alterations of toxicological importance were caused by MPE, as the organ–body weight ratio and serum/tissue indicators of organ function/damage were not adversely altered. In conclusion, MPE demonstrated inhibitory activity against both α-amylase and α-glucosidase, which may contribute to its potential hypoglycemic effects. Additionally, the findings indicate that the peel extract is non-toxic in rats following sub-acute administration at doses up to 400 mg/kg body weight. Further studies involving diabetic models and chronic exposure will substantiate and extend these preliminary observations. Full article

Objectives: One of the major trends in modern computational toxicology is the development of explainable predictive tools. However, the complex nature of the mechanistic representation of biological organisms and the lack of relevant data remain limiting factors. Methods: This work provides a publicly available dataset of 12,654 compounds with mouse intravenous ${\mathrm{LD}}_{50}$ values, as well as docking scores (Vina-GPU 2.0) against 44 toxicity-associated proteins. NIH and Brenk filters were applied to refine the chemical space. Results: Across the entire protein panel, the human ether-a-go-go–related gene channel (hERG/KCNH2), vasopressin receptor 1A (AVPR1A), the L-type voltage-gated calcium channel Cav1.2 (CACNA1C), the potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) and endothelin receptor A (EDNRA) showed the strongest association with acute toxicity. Statistically significant differences were found in the distribution of ${\mathrm{LD}}_{50}$ values for compounds that bind antitargets compared with non-binders. Using known bioactive molecules such as anisodamine, butaperazine, soman, and several cannabinoids as examples confirmed the effectiveness of inverse docking for elucidating mechanism of action. Conclusions: The dataset offers a resource to advance transparent, mechanism-aware toxicity modeling. The data is openly available. Full article

Permethrin (PERM) is a synthetic pyrethroid insecticide initially regarded as low risk. However, evidence now indicates that misuse and prolonged exposure can damage multiple physiological systems by disrupting enzymatic functions in subcellular structures. In this study, male Wistar rats were administered PERM (75, 150, or 300 mg/kg/day) for 15 days to assess its effect on hematological and biochemical parameters, including oxidative stress markers in the liver, kidney, and heart. Subacute PERM administration induced significant, dose-dependent toxicological alterations in exposed animals. Hematological analysis revealed impaired hematopoiesis, characterized by increased erythrocytes and platelets alongside decreased hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width. Biochemical analysis revealed elevated liver enzymes and bilirubin, along with reduced albumin levels, indicating hepatic alterations associated with PERM. The assessment of oxidative stress revealed tissue-specific responses following PERM exposure. While GPx, CAT, and SOD levels remained unchanged, GR activity increased in the heart, and GST activity increased in the liver. Additionally, a substantial decrease in MDA was observed in both the liver and heart. These collective alterations found in PERM-subacute exposed rats suggest the potential for cellular damage with the possible development of chronic pathologies, warranting further investigation. Full article

Combretum micranthum G. Don (kinkeliba) is a medicinal plant traditionally employed in West Africa for its diuretic and gastrointestinal therapeutic properties. Despite its extensive ethnomedicinal use, comprehensive toxicological assessments are still lacking. This study aimed to characterize the phenolic composition of C. micranthum ethanolic leaf extract using HPLC-DAD-ESI-MS and evaluate its acute and subacute oral toxicity in BALB/c mice, per OECD Guideline 420. Female mice received oral doses of 50, 300, and 2000 mg/kg of extract for acute toxicity assessment for 14 days. In the subacute study, both sexes were administered daily doses at the same concentrations over 28 days. Clinical signs, body weight, and food and water consumption were regularly monitored throughout both protocols. At the end of each study, hematological, biochemical, and histopathological parameters were analyzed. Phenolic profiling revealed nine major compounds with a total of 293.54 mg/g extract. No mortality or significant clinical manifestations were observed at any dose. However, significant variations in platelet counts and amylase activity were noted in the acute phase. In the subacute model, slight, non-critical alterations in hepatic and renal biomarkers were observed, without signs of systemic toxicity. Histopathological examination revealed similar lesions in both acute and subacute phases, including multifocal inflammatory infiltrates (lymphocytes and neutrophils) in the periportal area of the liver, minimal bacterial overgrowth in the superficial layer of the gastric mucosa, minimal medullary mineralization and inflammatory infiltrates with lymphocytes in the kidneys, and minimal to moderate vacuolization in the pancreatic acini. These results indicate that C. micranthum ethanolic extract is relatively safe at the tested doses, reinforcing its traditional use and supporting further research into its pharmacological potential. Full article

Ralstonia eutropha H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety evaluations remain insufficient for food-grade applications. This study systematically assessed the safety of R. eutropha H16 through genomic, phenotypic, and toxicological analyzes. Genomic analyzes revealed the absence or minimal presence of virulence factors and antibiotic resistance genes, aligning with microbiological safety standards. Phenotypic investigations demonstrated a limited gastric fluid tolerance (pH 2.5, survival rate 25.70% after 3 h) and intestinal fluid persistence (pH 8, 44.67% viability after 3 h), coupled with an exceptional bile salt tolerance (0.2% w/v). Antioxidant assays confirmed the fermentation broth specifically scavenges DPPH free radicals (14.60 ± 1.24 μg Trolox/mL), whereas bacterial suspensions and cell-free supernatants exhibited a strong hydroxyl radical scavenging (>90 U/mL) and superoxide anion inhibition (>100 U/L). Acute toxicity testing indicated no mortality or histopathological abnormalities, with an LD₅₀ value exceeding 1 × 10¹¹ CFU/kg. Subacute toxicity studies (28-day, 1 × 10⁸–1 × 10¹⁰ CFU/kg) revealed no significant effects on growth, hematology, or organ function. Minor alterations in serum biochemistry might be attributed to physiological adaptation. Subacute exposure induced transient serum ALT fluctuations without hepatorenal dysfunction, while maintaining hematological parameters within physiological ranges. Collectively, these results substantiate the safety of R. eutropha H16 for food-related applications while underscoring the necessity of strain-specific risk assessments for industrial microbial platforms. Full article

This study rigorously evaluated the safety profile of dietary fiber extracted from cassava pulp, a promising functional food ingredient, through acute and 28-day sub-acute oral toxicity assessments in Wistar rats. This research hypothesized that cassava pulp fiber would exhibit minimal toxicity across a range of doses. In the acute study, rats received single oral doses of 175, 550, or 2000 mg/kg, while the sub-acute toxicity study involved daily doses of 250, 500, or 1000 mg/kg, with satellite groups included for reversibility assessment. Comprehensive monitoring encompassed clinical signs, mortality, body weight, food intake, hematological and biochemical parameters, relative organ weights, and detailed histopathological examination. Remarkably, no treatment-related mortality or overt clinical signs of toxicity were observed in either study. The LD₅₀ was higher than 2000 mg/kg for the acute study and the no-observed-adverse-effect level (NOAEL) was determined to be 2000 mg/kg for the acute study and 1000 mg/kg for the sub-acute toxicity study, indicating a high margin of safety. While statistically significant alterations were noted in some hematological, biochemical, and relative organ weight parameters, these changes were not considered toxicologically relevant. Notably, histopathological changes in the lungs were observed across all groups, including controls, warranting further investigation. These findings suggest that cassava pulp fiber is well tolerated at high oral doses, supporting its potential for safe application in food and nutraceutical formulations. However, the observed lung alterations necessitate further research to elucidate their etiology and clinical significance. Full article

Duguetia furfuracea, “araticum-seco”, is known to contain several bioactive compounds that can mitigate oxidative stress and act on the central nervous system (CNS). This effect is partly attributed to its potent antioxidant and acetylcholinesterase (AChE) inhibitors. In this study, the effects were explored of the methanolic extract (MEDF) and alkaloid fraction (AFDF) of D. furfuracea (leaves) on cognitive behaviors in male mice with scopolamine (Scop)-induced cognitive impairment and biochemical parameters. Additionally, anxiolytic behavior, subacute toxicity, molecular docking and antioxidant activity were reported. MEDF (30, 100 or 300 mg/kg) or AFDF (30 mg/kg) were orally administered for 16 days and Scop (intraperitoneally, i.p.) between days 11 and 16. The anxiolytic behavior (open field test and marble burying) in healthy mice, and the Scop-induced memory impairment (object recognition test and Morris water maze (MWM)) were assessed, and the biochemical parameters (malondialdehyde (MDA) and AChE levels) were measured after euthanasia. The subacute toxicological impact of MEDF was assessed in female Swiss mice for 28 days. MEDF and AFDF were available for the DPPH, ABTS and β-carotene/linoleic acid models. The results revealed that MEDF and AFDF exhibit anxiolytic effects and significantly alleviated Sco-induced memory impairment, inhibited AChE in the cortex (40%) and MDA (51.51%) levels. Reticuline was reported in AFDF and molecular coupling with AChE involves link-type hydrogen bonds and van der Waals interactions. MEDF exhibited antioxidant capacity (DPPH, IC₅₀ = 18.10 ± 1.70 µg/mL; ABTS, IC₅₀ = 10.41 ± 1.69 µg/mL). MEDF did not reveal signs of toxicity. In conclusion, D. furfuracea shows promise in mitigating scopolamine-induced memory deficits, potentially because it inhibits AChE activity, reduces MDA levels, and enhances antioxidant activities. Full article

Background: A series of spiro-fused heterocyclic compounds containing cyclopropa[a]pyrrolizidine-2,3′-oxindole and 3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole frameworks were synthesized and studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), acute T cell leukemia (Jurkat), melanoma (Sk-mel-2) and breast cancer (MCF-7) as well as mouse colon carcinoma (CT26) cell lines. Methods: Cell proliferation was evaluated in vitro by MTS assay. Confocal microscopy was used to study actin cytoskeleton structure and cell motility. Cell cycle analysis was evaluated by flow cytometry. Results: It was found that compounds 4, 8, 18 and 24 showed antiproliferative activity against the Jurkat, K-562, HeLa and Sk-mel-2 cell lines with IC₅₀ ranging from 2 to 10 μM (72 h). Evaluation of the impact on cell cycle progression showed that the tested compounds achieved significant cell-cycle perturbation with a higher accumulation of cells in the SubG1 and G0/G1 phases of the cell cycle, in comparison to the negative control. I Incubation with tested compounds led to the disappearance of stress fibers (granular actin was distributed diffusely in the cytoplasm in up to 38% of treated HeLa cells) and changes in the number of filopodia-like deformations (reduced from 93% in control cells to 64% after treatment). The impact on the Sk-mel-2 cell actin cytoskeleton structure was even greater: granular actin was distributed diffusely in the cytoplasm in up to 90% of treated cells while the number of filopodia-like deformations was reduced by up to 23%. A scratch test performed on the human melanoma cell line showed that these cells did not fill the scratched strip and lose their ability to move under treatment. Conclusions: The obtained results support the antitumor effect of the tested spiro-compounds and encourage the extension of this study in order to improve their anticancer activity as well as reduce their toxicological risks. Full article

The presence of sub-micron-sized plastics in the environment has been increasing, with the possible risks of these particles remaining relatively unknown. In order to assess the toxicity of these particles, 100 nm diameter green fluorescent nano-polystyrene spheres (NPS) (20–60 mg/L) were exposed to zebra mussels (Dreissena polymorpha) to investigate the mortality, clearance rate and stress-related biomarker responses. D. polymorpha were collected and analysed with standard OECD toxicological tests and biomarker analysis to detect both physical and biochemical responses after exposure to NPS. The toxicity of the NPS to D. polymorpha was low, with 60 mg/L NPS causing a mortality rate of 11.1% at 96 h which was statistically significant compared to the 4.2% control. No statistical change could be found for the condition factor (k_c) of D. polymorpha after NPS exposure. Clearance rates in D. polymorpha using R. subcapitata algae showed NPS-exposed mussels had a reduction of filtering efficiency of up to 30.5%. Bioassay testing shows a mixed but undeniably negative response from the D. polymorpha to the NPS, notably a significant rise in DNA Strand Breaks (DSB) and Metallothionein (MT) responses for high NPS concentrations. Additionally, Lipid Peroxidation (LPO) and Ferric Reducing Antioxidant Power (FRAP) assay tests showed a significant increase in response from the higher (>40 mg/L) concentrations of NPS exposure. Although Glutathione S-Transferase (GST) assay showed no statistical change from the control for all NPS-exposed samples, an increase of 20% had occurred for 60 mg/L NPS. Overall, a minimal toxic response from D. polymorpha to the NPS exposure below 40 mg/L was seen. After 40 mg/L NPS, mussels presented more acute toxicity in terms of mortality, along with reduced algal clearance rates and anincrease in biomarker response. This study revealed a clear induction of oxidative stress and DSB in the digestive gland of zebra mussels following exposure to nano-polystyrene. While these findings provide valuable insights into the potential harmful effects of nanoplastics in freshwater bivalves, further studies are necessary to help understand the level of threat plastic pollution may pose to the health of freshwater ecosystems. Full article

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart. Full article